Can digital health apps provide patients with support to promote structured diabetes education and ongoing self-management? A real-world evaluation of myDiabetes usage.

Objective: Structured diabetes education has evidenced benefits yet reported uptake rates for those referred to traditional in-person programmes within 12 months of diagnosis were suboptimal. Digital health interventions provide a potential solution to improve diabetes education delivery at population scale, overcoming barriers identified with traditional approaches. myDiabetes is a cloud-based interactive digital health self-management app. This evaluation analysed usage data for people with type 2 diabetes focusing on digital structured diabetes education. Methods: Descriptive quantitative analyses were conducted on existing anonymised user data over 12 months (November 2019-2020) to evaluate whether digital health can provide additional support to deliver diabetes education. Data was divided into two equal 6-month periods. As this overlapped the onset of COVID-19, analyses of its effect on usage were included as a secondary outcome. All data was reported via myDiabetes. Users were prescribed myDiabetes by National Health Service healthcare primary care teams. Those who registered for app use within the study period (n = 2783) were assessed for eligibility (n = 2512) and included if activated. Results: Within the study period, n = 1245/2512 (49.6%) registered users activated myDiabetes. No statistically significant differences were observed between gender (p = 0.721), or age (p = 0.072) for those who activated (59.2 years, SD 12.93) and those who did not activate myDiabetes (57.6 years, SD 13.77). Activated users (n = 1119/1245 (89.8%)) viewed 11,572 education videos. No statistically significant differences were observed in education video views across age groups (p = 0.384), gender (p = 0.400), diabetes treatment type (p = 0.839) or smoking status (p = 0.655). Comparison of usage pre-COVID-19 and post-COVID-19 showed statistically significant increases in app activity (p ≤0.001). Conclusion: Digital health is rapidly evolving in its role of supporting patients to self-manage. Since COVID-19 the benefits of digital technology have become increasingly recognised. There is potential for increasing diabetes education rates by offering patients a digital option in combination with traditional service delivery which should be substantiated through future research.

Internalization and intracellular processing of bone morphogenetic protein (BMP) in rat skeletal muscle myoblasts (L6).

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily capable of inducing bone and cartilage formation in ectopic extraskeletal sites and transducing their effects through binding to serine-threonine kinase receptors. In this study, the fate of 125I-labelled native BMP after binding to cell surface receptors on L6-myoblasts was examined with both continuous and intermittent exposure of the ligand. BMP was readily internalized in L6 cells at +37 degrees C, and the internalization reached a plateau in 2 h. Intracellular degradation of 125I-labelled BMP was established, and degradation products were also detected in binding buffer, indicating exocytosis of the processed ligands. BMP receptors were shown to be subject to acute down-regulation by the ligand, and receptors were completely recycled in 3 h. Hence, we conclude that BMP receptors, like receptors for various other polypeptide ligands, have the ability to mediate intracellular delivery and degradation of the ligand.

Alexithymic features in relation to the dexamethasone suppression test in a Finnish population sample.

Hypothesizing that a positive DST result could reflect an aberrant stress reaction in subjects with alexithymic features, the authors investigated the relationship between alexithymic features and DST results in 266 subjects from a Finnish adult population sample. Alexithymic features were assessed with the Beth Israel Questionnaire. The authors found a statistically significant association between observed alexithymic features and a positive DST result. This association could be seen after adjustment separately for age, social rank, marital status, and the occurrence of depression.

Human fetal dopamine neurons grafted into the striatum in two patients with severe Parkinson's disease. A detailed account of methodology and a 6-month follow-up.

By using stereotaxic surgical techniques, ventral mesencephalic tissues from aborted human fetuses of 8 to 10 weeks' gestational age were implanted unilaterally into the striata in two patients with advanced Parkinson's disease. The patients were treated with a cyclosporine, azathioprine, and steroid regimen to minimize the risk for graft rejection. They were examined for 6 months preoperatively and 6 months postoperatively and continued to receive the same doses of antiparkinsonian medication. There were no significant postoperative complications. No major therapeutic effect from the operation was observed. However, in the clinical tests, both patients showed small but significant increases of movement speed for repeated pronation-supination, fist clenching, and foot lifting. The rate of walking also increased in the one patient tested. For both patients, there was an initial worsening postoperatively, followed by improvement vs preoperative performance at 1 to 3 months. Both patients also showed significant improvement in the magnitude of response to a single dose of levodopa (L-dopa), but there was no increase in the duration of drug action. The motor readiness potential increased in both patients postoperatively, primarily over the operated hemisphere. Neurophysiological measurements also showed a more rapid performance of simple and complex arm and hand movements on the side contralateral to transplantation in one patient at 5 months postoperatively. Positron emission tomography demonstrated no increased uptake of 6-L-(18F)-fluorodopa in the transplanted striatum at 5 and 6 months. Taken together, these results suggest that the fetal nigral implants may have provided a modest improvement in motor function, consistent with the presence of small surviving grafts. Although our results support further scientific experimentation with transplantation in Parkinson's disease, widespread clinical trials with this procedure are probably not warranted at this time.

Time-related deviations of fibronectin and type I, II and III collagen on the interface between a hydroxyapatite disc and the rim of a calvarial trephine defect in rabbits.

To pursue the events around hydroxyapatite (HA) discs (diameter 9 mm), implanted in calvarial defects in rabbits (diameter 11 mm), immunohistochemical changes of fibronectin and type I, II and III collagen were quantitatively determined in the connective tissue-HA (CTHA) and host bone-HA (BHA) interface at 8, 12 and 16 wk postimplantation. A marked enhancement of type I collagen staining in the BHA interface was noted at the 12th and the 16th wk in comparison to the CTHA interface and connective tissue in the untreated control defect. However, one of the characteristics of the staining in the CTHA interface was the finding of exceptionally high fibronectin and type III collagen at the 8th and the 12th wk in contrast to the BHA interface and the untreated control defect. The change in these immunohistochemically determined compositions was probably due to an active proliferation of vascular components in the CTHA interface. Bone regeneration in the CTHA interface was parallel to an increase in type I collagen and a decrease in fibronectin and type III collagen from 8 to 16 wk. This study indicated that variances in composition or characteristics of connective tissue in CTHA interface have taken place ahead of bone morphogenesis. The time-related derivation of connective tissue matrix components in the BHA and CTHA interface was confined to the interaction of implanted HA with host tissues in contact with the implant.

Microscopic evaluation of bone-implant contact between hydroxyapatite, bioactive glass and tricalcium phosphate implanted in sheep diaphyseal defects.

In order to compare morphological discrepancies in bone-implant contact in vertebrates, cylinders of hydroxyapatite, bioactive glass and tricalcium phosphate were implanted in segmental defects of the tibia in sheep. Three types of visible bone-implant contact were observed microscopically at 4 months after implantation. The trabecular web-like bone-implant contact noted in tricalcium phosphate seemed superior to the disseminated patchy bone-implant contact in bioactive glass and the buttressed bone-implant contact in hydroxyapatite with respect to both bone ingrowth and bioresorption of the implant. Differences of physicochemical properties on the surface among the three kinds of bioceramic implants probably give rise to different types of bone-implant contact.

Morphological and biomechanical difference in healing in segmental tibial defects implanted with Biocoral or tricalcium phosphate cylinders.

To evaluate the effects of two bioceramics on bone regeneration during repair of segmental bone defects, Biocoral and tricalcium phosphate cylinders were implanted in osteotomized sheep tibial defects 16 mm in length and followed up for 16 weeks. In comparison with the TCP-implanted defect, a significant increment in area and density of external callus was quantified radiomorphometrically at 3 weeks, and a marked increase in maximal torque capacity, maximal angle of deformation and absorption of energy was demonstrated mechanically in the Biocoral-implanted tibia at 16 weeks after implantation. Better bone integration with the substratum was microscopically observed in Biocoral cylinders. With good osteointegration and biomechanical-performance, Biocoral seems to be superior to TCP in repair of segmental defects in weight-bearing limbs.

Expression of tenascin R and J1 mRNA in motoneurons after a traumatic lesion in the spinal cord.

We demonstrate, using in situ hybridization, that mRNA for the anti-adhesive molecules tenascin R and J1 in the adult rat spinal motoneurons are down-regulated rapidly as a reaction after a ventral funiculus lesion. Tenascin-R was significantly down-regulated at day 1 and normalized after 3 weeks. Tenascin-J1 declined to its lowest value at day 3 and returned to the initial level after 3 weeks. In adjacent sections, the distribution of macrophages was studied with immuno histochemistry. The density of macrophages reached a maximum 3 days after the injury. Thus, the density of macrophages appeared to be inversely related to the level of tenascin mRNA. These data are compatible with the notion that neuronal tenascins may modulate the adhesion of perincurial inflammatory cells.

Semaphorin and neuropilin expression in motoneurons after intraspinal motoneuron axotomy.

We have examined mRNA and protein distribution for the axon guidance molecules semaphorin3A, 3F, 4F and semaphorin receptors neuropilin-1 and 2, 1-21 days after intramedullary axotomy of rat lumbar spinal cord motoneurons. We show that semaphorin3A mRNA and protein are up-regulated in the scar and in motoneurons from 3 days and upto 3 weeks after injury. Neuropilin-1 mRNA showed no changed expression in axotomized motoneurons. Semaphorin3F mRNA expression was found in ventral roots after ventral funiculus lesion (VFL) and neuropilin-2 mRNA was found in affected motoneurons from 1 day after injury throughout the examined period. Semaphorin4F mRNA was first found in motoneurons 3 weeks after lesion. These results suggest semaphorin/neuropilin involvement in the injury response of intramedullary axotomized motoneurons.

Neonatal sciatic nerve transection induces TUNEL labeling of neurons in the rat spinal cord and DRG.

Transection of a peripheral nerve in neonatal rats induces an extensive death of axotomized neurons. We demonstrate here that spinal motoneurons and sensory dorsal root ganglia neurons become TUNEL-labeled after sciatic nerve transection in neonatal rats, thus indicating that apoptotic mechanisms are involved in the death process. Interestingly, there is also a profound increase of TUNEL-labeled interneurons in the deep dorsal horn. This location suggests that an intact afferent input and/or contact with target cells is essential for interneuronal survival. Death of motoneurons and sensory neurons could be a result of the injury per se and/or the deprivation of neurotrophic substances, secondary to the loss of contact with target cells.

trkC expression in the injured rat spinal cord.

Reactive non-neuronal cells express high levels of low-affinity neurotrophin receptor and truncated trkB receptors after spinal cord injury. Here we report that descending nerve fibres in the rat lateral spinal cord column show strong trkC-like immunoreactivity after traumatic spinal cord lesions in the adult rat. No change in trkC expression by glial cells could be detected by immunohistochemistry or in situ hybridization at the lesion site. The data suggest that regeneration of descending spinal cord axons could be encouraged by the trkC ligand, neurotrophin 3.

Permanent open shunt as a reason for impotence or reduced potency after surgical treatment of priapism in 26 patients.

A permanent open shunt as a cause of impotence or impaired potency after a shunt operation for priapism is an unusual situation. In this series we studied the persistence of an open shunt in 26 patients who had developed impotence or impaired potency after operative treatment for priapism. All patients had been examined by cavernosography on the suspicion of an open shunt, giving a positive finding in five of 26 cases, in all of which impotence was cured by closure of the shunt. In five patients without a permanent open shunt potency returned to normal only after 6-12 months.

Use of myoblasts in assaying the osteoinductivity of bone morphogenetic proteins.

A novel, time- and BMP-saving in vitro method for the detection and quantitation of bone morphogenetic protein (BMP) activity was developed based on the measurable effects of BMP on rat skeletal muscle myoblasts (L6). Calcium incorporation, stimulation of alkaline phosphatase activity and production of osteocalcin were used as markers of bone cell metabolism and on-going morphogenesis. The morphological change was confirmed by Chlorantine fast red and von Kossa staining. The response of various BMPs was purity-dependent and consistent with intramuscular implantations of the same materials. Neither TGF-beta1 nor insulin could induce the same actions. The data from this study indicate that at least in part in vivo implantations of BMP extracts can be replaced by in vitro measurement of osteoinductivity. Considerable saving of time, BMP and experimental animals can be achieved using cell culture conditions for the determination of bone-forming activity.

The role of transforming growth factor-beta on retarded osteoblastic differentiation in vitro.

Various matrix growth factors play important roles in the development and growth of cartilage and bone. Among them transforming growth factor-beta superfamily and especially bone morphogenetic proteins are known to be important factors, since they induce bone and cartilage formation in ectopic sites in vivo. We have previously shown that the human osteosarcoma cell line Saos-2 expresses molecules that in vivo induce new bone formation with asymmetric bone maturation. In this study we examined the role of Saos-2-conditioned medium in prolonged cultures of mesenchymal C3H/10T1/2 cells. The C3H/10T1/2 cells were cultured with Saos-2-conditioned medium for 28 days. We show that Saos-2-treated C3H/10T1/2 cells performed retarded osteoblastic differentiation when compared to recombinant BMP-2 and -4 induced differentiation. We further show that this retardation is due to excessive amounts of transforming growth factor-beta in Saos-2-conditioned medium. Our results also suggest that this model can well be used to study additional cofactors involved in retarded osteogenesis.

Image processing for femoral endosteal anatomy detection: description and testing of a computed tomography based program.

A computed tomography (CT)-based image processing computer program was developed for three-dimensional (3D) femoral endosteal cavity shape modelling. For the examinations 50 cadaver femora were used. In the CT imaging 30 axial slices were taken above and below the lesser trochanter area from each femur. Different image analysis methods were used for femoral cavity detection depending on the structure of the processed slice. In the femoral shaft area simple thresholding methods succeeded, but in the problem areas of the metaphyseal femur edge, detection operators and local thresholding were required. In contour tracking several criteria were used to check the validity of the border pixels. The results were saved as four output data files: (i) a file for the longest anteroposterior (ap), mediolateral (ml) and oblique diameters computed by a Euclidian method, (ii) and (iii) files for 2D and 3D data respectively, and (iv) a file for centre points of each slice. Finally, testing of the results and dimensions obtained from the image analysis were carried out manually by sawing the femora into 10 stipulated horizontal slices. The ap and ml dimensions were measured with a caliper ruler. The CT-based image processing yielded a peak distribution of dimensions with a negative difference to those obtained in manual measurements. The mean difference between the image processing and the manual measurements was 1.1 mm (+/-0.7 mm, +/-1 SD). The difference was highest in the proximal slices of the femora of group I (with lowest cortical thickness), i.e. 1.3 mm (+/-0.8 mm) and lowest in the distal slices of the femora from group III (with highest cortical thickness), i.e. 0.9 mm (+/-0.6 mm). The results are acceptable for further use of the program to study endosteal anatomy for individual femoral component selection and designing basis.

Aggressive granulomatous lesions associated with hip arthroplasty. Immunopathological studies.

The local immunopathological response was analyzed in six patients who had a revision of a total hip prosthesis because of an aggressive granulomatous lesion and in six patients who had a revision because of common loosening of the prosthetic stem. All twelve patients had had a total replacement arthroplasty for primary osteoarthrosis. All of the prostheses had been cemented. The aggressive granulomas consisted of well organized connective tissue containing histiocytic-monocytic and fibroblastic reactive zones. The granulomas were highly vascularized, and villous structures were observed at many sites. In contrast, the areas around the loose cemented stems were characterized by dense connective tissue. Immunohistological evaluation revealed that most of the cells in the aggressive granulomatous tissue were multinucleated giant cells and C3bi-receptor and nonspecific esterase-positive monocyte-macrophages. This cytological finding suggests a foreign-body-type reaction, compatible with the rapidly progressive lytic nature of the lesion that was shown radiographically. There was a clear-cut difference between aggressive granulomatosis and the more common lesion accompanying prosthetic loosening--namely, the relative lack of activated fibroblasts in granulomatosis. We suggest that granulomatosis involves an uncoupling of the normal sequence of monocyte-macrophage-mediated clearance of foreign material and tissue debris that is normally followed by fibroblast-mediated synthesis and remodeling of the extracellular matrix. We also suggest that aggressive granulomatosis in association with a cemented hip prosthesis is a distinct entity, not only clinically and radiographically, but also histopathologically.

Induction of new-bone formation in the host bed by human bone-tumor transplants in athymic nude mice.

UNLABELLED: Specimens of twelve osteosarcomas, five chondrosarcomas, one giant-cell tumor, and five extraskeletal soft-tissue sarcomas were transplanted into male athymic nude (nu/nu) mice. Survival of the transplant was determined by the volume-doubling time and the sex chromatin of the tumor cells obtained from two female patients. By these criteria and the similarity of the histological composition of the original tumor and the transplant, survival occurred in four of twelve osteosarcomas and four of five chondrosarcomas. Without any local infiltration of lymphocytes or plasma cells, or other evidence of cell-mediated immunity, the surviving tumors regressed by the fourth week after the operation. Transformed osteoblasts and osteoprogenitor cells were replaced by fibrous connective tissue or fibrogenic tumor-tissue cells. Osteocytes degenerated and disappeared from the lacunae. The one giant-cell tumor transplant survived, growing very slowly, but by the end of the first week after transplantation whorls of mononucleated cells appeared in sites previously occupied by multinucleated cells. Transplants of leiomyosarcoma, liposarcoma, and synovioma (one tumor of each) degenerated. One of two fibrosarcomas survived transplantation. The most striking reaction of the mouse host bed was to encompass six of twelve osteosarcomas and four of five chondrosarcomas in deposits of normal living cartilage, bone, and bone marrow. The incidence of new bone inducedy by living transplants was only slightly greater than by implants of freeze-dried killed osteosarcoma tissue. Not one of five extraskeletal sarcomas, living or dead, induced bone formation. These observations suggest that an osteoinductive agent is transmitted by some osteosarcomas and chondrosarcomas. This agent initiates differentiation of host mesenchymal cells into normal non-tumorous cartilage and bone, which later colonized by bone marrow. CLINICAL RELEVANCE: Our observations present experimental evidence of the origin of the envelope of normal non-tumorous bone that may surround tumorous bone. In 1926, Phemister recognized the clinical significane of this envelope as a pitfall in the differential diagnosis of malignant bone tumors, chondrosarcoma, myositis ossificans circumscripta, and other neoplasms. He emphasized the importance of examining the entire specimen for the distribution of deposits of tumorous and normal bone. The induction of normal bone formation in the host bed surrounding transplants of osteosarcomas and some chondrosarcomas (but not transplants of fibrosarcoma, liposarcoma, or leiomyosarcoma) is evidence of a specific tumor-cell characteristic. Thus, the bone inductive response is not an unspecific reaction to injury from expansion or of tumor growth but a biological response to tumor-cell products. Transplants of human malignant tumors growing in the thymus-deficient mouse can be treated by combinations of radiation, amputation, and new chemotherapeutic agents...

Self-perceived fatigue and cortisol secretion in a community sample.

The possible relation of cortisol secretion to self-perceived fatigue was examined in an adult community sample. Serum cortisol levels measured after the dexamethasone suppression test (DST) did not predict fatigue whereas depression assessed by the Beck Depression Inventory (BDI) and current medical treatment were significant and independent predictors. Confounding variables such as age, gender, body mass and social status were not predictive of fatigue. Of putative hypothalamic-pituitary-adrenal abnormalities hypersecretion of cortisol does not typify subjects with self-perceived fatigue.

Plasma concentrations of vitamin C, vitamin E and/or malondialdehyde as markers of oxygen free radical production during hemodialysis.

To investigate the effects of neutrophil activation during hemodialysis (HD), blood markers of oxygen free radical (OFR) activity were studied. Two groups of HD patients on standard cuprophane treatment were investigated after an overnight fast. In the first group (mean age 68 +/- 8 years; n = 6) vitamin supplementation was withdrawn two weeks prior to the study, whereas the second group (mean age 73 +/- 3 years; n = 7) continued their normal vitamin intake. The two control groups, one consisting of age-matched subjects (mean age 72 +/- 2 years; n = 21), the other of younger subjects (mean age 36 +/- 7 years; n = 11), were asked to cease vitamin supplementation two weeks before the study and to fast overnight before blood sampling. Serial blood and dialysate samples were collected during HD in the vitamin-deprived patient group, and a single blood sample was collected in the other three groups. Plasma concentrations of vitamin C (total and reduced form), vitamin E (alpha-tocopherol) and malondialdehyde (MDA) were determined with newly adopted and validated HPLC methods. Basal plasma vitamin C concentrations were lower among vitamin-deprived HD patients than among age-matched controls or vitamin-supplemented HD patients (22 +/- 6 microM versus 39 +/- 19 microM and 34 +/- 10 microM, respectively). During a 3-hour HD session, the mean decrease in total vitamin C was 40%. Basal alpha-tocopherol concentrations did not differ significantly between vitamin-deprived HD patients and vitamin-supplemented HD patients or age-matched controls (39 +/- 5 microM versus 40 +/- 11 microM and 38 +/- 6 microM, respectively), but were lower in younger controls (33 +/- 4 microM). No alpha-tocopherol was detected in the dialysate, and its plasma concentration did not change significantly during a single HD session. Basal plasma MDA concentrations were higher in vitamin-supplemented HD patients than in vitamin-deprived HD patients or age-matched controls (1.5 +/- 0.2 microM versus 0.9 +/- 0.2 microM and 1.1 +/- 0.2 microM, respectively). No MDA was detected in the dialysate, and its plasma concentration did not change significantly during a single HD session. Our results indicate an increased need of vitamin C supplementation in HD patients. The concentration of oxidized vitamin C seems to peak early during HD and may be of value as a marker of OFR production. alpha-tocopherol concentrations do not change during HD and do not differ from those in control subjects. MDA may increase over a longer period of time on dialysis, but does not change during a single HD treatment.

Radiographic changes of the revascularized femoral head.

Twenty-two necrotic femoral heads in young adults were radiologically followed-up after grafting with vascularized bone by comparing the preoperative and the postoperative state of the hip joint. Three parameters were observed and followed; the flattening of the femoral head; the degree of osteoarthrosis of the joint; and the degree of incorporation of the graft into the recipient bone. The results, expressed by index figures, showed that the femoral head flattened during the first two years postoperatively; that the maximal incorporation occurred during the same period of time; and that the appearance of postoperative osteoarthrosis was slow during the first year and increased subsequently. This numerical characterization of radiological findings allows systematic individual analysis after revascularization of the femoral head with bone grafts. It is also suited for comparisons between patients, between series of patients and of various treatment techniques. Furthermore, this quantification provides a numerical index that seems to correlate with the outcome of the treated hip joint.